Metalloproteinase-13 is the major type II collagenase that directly implicates cartilage matrix destruction. Metalloproteinase-13 is inducted and activated by interleukin-1 β, which is a commonly observed proinflammatory cytokine in the joint cavity of arthritic patients. Depression of interleukin-1 β function can inhibit metalloproteinase-13 expression and protect the cartilage extracellular matrix. In this study, resveratrol release microspheres were developed, and the direct function of the released resveratrol on the interleukin-1 β was discussed. The resveratrol-loaded microspheres were fabricated using oil-in-water emulsion and solution-evaporation methods. The particle size and the encapsulation efficiency for the techniques, which used different fabrication conditions, were within 8.3–63.9 μm and 37%–82%, respectively. The effect of drug release lasted for more than 650 h in a PBS solution at 37℃. Human bone mesenchymal stem cells were chosen for cell experiments. Interleukin-1 β was used to induce an inflammatory condition. The effect of sustained resveratrol release from the microspheres on the cells' gene expression was observed using the transwell co-culturing method. The results indicated that metalloproteinase-13 mRNA expression was upregulated after interleukin-1 β induction. The released resveratrol directly inhibited the function of interleukin-1 β and thus downregulated metalloproteinase-13 mRNA expression. Moreover, the upregulation of Col2, aggrecan and Sox9 mRNA expressions, which are major chondrocyte markers, was observed after resveratrol was released into the culture medium. Resveratrol was observed to maintain the cells' chondrogenic gene expression when subject to the inflammation condition. The sustained released resveratrol inhibited interleukin-1 β-inducted metalloproteinase-13 activation and promoted chondrocyte differentiation. This drug-loading microsphere is a promising candidate for arthritis therapy.